Blood sedimentation apparatus



June 7, 1966 H. G. NOLLER V BLOOD SEDIMENTATION APPARATUS Filed April 29, 1963 Jnvenlar: HANS e UNTER NciLLsR a Ila/U1 50m A 6ENT United States Patent 3,254,527 BLOOD SEDIMENTATION APPARATUS Hans Giinter Niiller, Fasanenweg 4, Heidelberg, Germany Filed Apr. 29, 1963, Ser. No. 276,527 Claims priority, application Germany, May 3, 1962, N 21,537 Claims. (Cl. 73--61) This invention relates to apparatus for blood analysis, and more particularly to an apparatus for determining the erythrocyte sedimentation rate (ESR) in human and other'blood.

The erythrocyte sedimentation rate is a valuable index of body functions, and is performed on many hospital patients at relatively frequent intervals. The human labor necessary for performing routine ESR tests in hospitals is costly and not always readily available. The ESR readings obtained by relatively unskilled and/or overworked personnel are not always reliable. The results of conventional ESR tests are available only after a relatively long waiting time.

The object of the invention is the provision of blood sedimentation apparatus which reduces the functions of a human operator in an ESR test to a minimum.

Another object is a reduction in the time required between the preparation of a specimen and the reading of the ESR value which permits the test to be perforn1 ed in the time normally assigned to a medical routine examination, say fifteen minutes or less.

Yet another object is the provision of an apparatus automatically yielding ESR values equivalent to the conventional l-hour, 2-hour, and/or 24-hour readings from a single specimen upon the pressing of a single button, in a few minutes.

An additional object is the provision of an ESR ap-- paratus which furnishes data independent of ambient temperature, and thus makes it unnecessary to correct the ESR values obtained for deviations from a standard temperature.

' It is well known that the electrolytic conductivity of human blood plasma is virtually constant, and does not vary significantly from one human being to the other. erythrocytes have a conductivity so much lower than that of the plasma that they may be considered non-conductors. I have found that the sedimentation of theerythrocytes changes the conductivity of an upright column of blood, and that data indicative of the sedimentation rate can be derived from measured conductivity changes.

The apparatus of the invention, in its basic aspects, consists of a container, preferably vertically elongated, of at least two electrodes in the container vertically spaced from each other and from the container bottom, and

The

If the higher electrode is located at a distance below the level of the blood specimen, and the lower electrode is relatively close to the bottom of the container, an increase in resistance is first observed when the erythrocytes originally present above the higher electrode drop into the area of resistance measurement at a higher rate than a corresponding number of erythrocytes can leave the area in a downward direction because of incipienttight packing of erythrocytes at the container bottom. The increase in resistance that can be observed with electrodes positioned in the manner described is of greater magnitude with a blood of high hematocrit value than with a blood of lowerhematocrit value.

The exact nature of-this invention as well as other objects and advantages thereof will be readily apparent from consideration of the following specification relating to the annexed drawing in which:

FIG. 1 is a perspective view of an ESR apparatus of the invention; and

FIG. 2 is a wiring diagram of the apparatus of FIG..1.

Referring initially to FIG. 1, there is seen an upright glass tube I mounted in a base 2. An electrode assembly 3 is inserted into the tube 1 and closes the top thereof.

circuitry connected to the electrodes and adapted to generate a perceptible signal when the resistance between the electrodes drops to a predetermined value. The time elapsed between the insertion of a blood sample into the container and the generating of the signal is inversely related to the ESR in millimeters per hour, or similar units.

The resistance of the, blood sample between the electrodes is generally at a maximum when the sample is poured into the container, and is constant as long as the space between the electrodes is filled with a normal distribution of plasma and erythrocytes. When all erythrocyteshave dropped to a level below the lower electrode, and the space betweenthe electrodes is occupied by plasma alone, the resistance between the electrodes reaches a stable minimum. When the electrical resistance between The electrode assembly consists of three conductors insulated from each other and mounted in a common holder which fits the tube 1 to position the exposed terminal portions of the conductors at precisely determined levels in the tube 1. The electrode assembly is connected by a cable 4 to an instrument housing 5. The dials of two counters may be viewed through two windows 6 in the housing 5. A push button switch 7 actuates the instrument, as will presently become apparent. Knobs 8 on the housing are provided for adjustment of variable circuit elements. A filling level is indicated by a mark 9 on the tube 1.

FIG. 2 shows the wiring diagram of the instrument contained within the housing 5 and of the connected electrode assembly. The circuit arrangement mounted in the housing 5 consists of four units A, B, C, and D which will be discussed in more detail hereinafter, of a 12 volt dry-cell battery 10, of two thermistors 11, 12, and of conductors connecting the circuit arrangement to the electrodes 13, 14, 15 of the electrode assembly 3.

The battery 10 energizes the transistorized circuits of the units A, B, C, and D. Unit D includes transistors Tr Tr which are elements of an astable multivibrator stage and generate an alternating low frequency square wave voltage which is fed to an amplifier stage including a transistor Tr The output of the unit D is fed to two voltage dividers. One voltage divider consists of the v I The unit A has a first secti-on including two transistors Tr Tr which constitutes a Schmitt trigger responsive to a predetermined voltage at the tap 16. The signal of the trigger controls an amplifier section including the transistor Tr A counter 18 is arranged in the collector lead of the transistor Tr The group B correspondingly has a Schmitt trigger section including transistors Tr, and Tr and connected to the tap 17, and an amplifier section including a transistor Tr energizing a counter 19.

The unit C constitutes a low frequency oscillator having transistors Tr and Tr which generate pulses at a constant low frequency. The pulses are fed to the amplifier sections of units A and B, and are amplified by the transistors Tr and Tr if the corresponding Schmitt triggers are in the appropriate stable condition.

Patented June 7, 1966 The circuit illustrated operates as follows:

The voltage generated by the multivibrator unit D produces an alternating potential at the taps 16 and 17 which is a function of the resistance of the blood columns between the electrodes 13, 14 and 14, 15 respectively, and of the resistance of the thermistors 11, 12. The temperature characteristics of the thermistors are selected to compensate for the known thermal variation in the resistance of blood plasma.

The input signals received from the taps 16, 17 are rectified in the Schmitt trigger circuits of units A, B by rectifiers 20, 21. The magnitude of the rectified input signals at which the triggers are operated may be set by means of variable resistors 22, 23 in the emitter leads of the transistors Tr Tr and Tr,;, Tr The resistors are operated by means of corresponding knobs 8 on the housing 5.

The erythrocyte sedimentation rate is determined by means of the illustrated apparatus in the following manner:

The blood specimen to be tested is mixed with citrate solution and with polyvinyl alcohol or a similar sedimentation accelerator in the usual manner, and the tube 1 is filled with the mixture to mark 9. The electrode assembly 3 is inserted in the tube, and the push button 7 is depressed, thus starting the pulse generating oscillator unit C. The pulses emitted by the unit C are recorded by the counters 18, 19 until the resistances between the electrodes 13, 14 and 14, 15 drop to respective values predetermined by the setting of the resistors 22, 23. At these resistance values, the Schmitt triggers are operated to block further transmission of pulses through the amplifying transistors Tr Tr and the counters are stopped.

It the counters are of the conventional type which emits a clicking sound while operating, the stopping of the sound will attract the operators attention, and a reading may be taken at the appropriate window 6 in units of time elapsed between the starting of the test and the automatic stopping of the couner. Obviously, the reading may be taken at any time after stoppage of the counter without introducing an error. This is an important advantage over the conventional ESR test in which readings obtained later than at the prescribed moment cannot usually be correlated with the desired result.

The illustrated apparatus of the invention is provided with electrodes defining two areas of resistance measurement at different levels. A resistance measurement taken with the electrodes 13, 14 near the mark 9 yields a time reading on the counter 18 which is inversely related to the results of a one-hour Westergren test in millimeters per second. The time reading in itself is a useful index of ESR, and may be converted to corresponding values on the Westergren scale by conversion charts or graphs obtained by calibration of the instrument for dimensional relationships. Temperature variations are automatically compensated for if the blood specimen is cooled to ambient temperature prior to the beginning of the test, as is virtually inherent in the operation of the apparatus.

The second counter 19 gives a time reading which is influenced by the afore-described packing of erythrocytes near the bottom of the tube 1 in a manner closely analogous to the conventional two-hour reading of sedimentation rate, and the readings on the counter 19 may be converted to two-hour readings by means of conver sion charts or calibration curves obtained by comparison tests with conventional devices.

While the instrument illustrated has three electrodes connected to two sets of trigger circuits and counters, more electrodes may be employed, and may be connected with additional units to give readings corresponding to other conventional tests such as a 24 hour ESR test.

The sensitivity of the Schmitt triggers to resistance variation is very high. With suitable calibration, even the equivalents of two-hour and twenty-four hour ESR tests may be performed in a fraction of an hour and in less than an hour respectively. The usual one-hour test value is readily obtained within a few minutes. It is entirely practical for the physician to take a blood specimen and to obtain a reading in the course of a routine examination.

The transistorized instrument and its battery can be enclosed in a housing 5 having the external dimensions of three superimposed packs of cigarettes and weighing only a few pounds together with its contents. In view of the rapid rate at which sequential tests can be performed with the apparatus, it is practical for hospital personnel to perform the test at the patients bedside immediately after withdrawing a blood specimen. Errors due to the time elapsed between the taking of the specimen and the performing of the test may thus be avoided.

The electronic apparatus illustrated in FIG. 2 measures the time elapsed from the beginning of the test to a predetermined drop in the erythrocyte level. The time reading obtained is indicative of the sedimentation rate. While such a method of measuring ESR is preferred because of its simplicity, it is evident that the change in the resistance of a column of blood during sedimentation of the erythrocytes may yield other signals equivalent to the results of a conventional ESR test.

As was mentioned hereinabove, the electrode may be connected to a recording ohmmeter, and the slope of the resistance record produced is directly related to ESR. Other arrangements will readily suggest themselves to those skilled in the art.

It should be understood, therefore, that the foregoing disclosure relates to only a preferred embodiment of the invention, and that it is intended to cover all changes and modifications of the example of the invention herein chosen for the purpose of the disclosure which do not constitute departures from the spirit and scope of the invention set forth in the appended claims.

What I claim is:

1. An apparatus for determining the erythrocyte sedimentation rate of blood comprising, in combination:

(a) two electrodes;

(b) mounting means for mounting said electrodes in a container containing said blood at predetermined vertically spaced levels; and

(c) signal generating means responsive to a predetermined electrical resistance between said electrodes for generating a signal, said signal generating means including l) a pulse generator for generating timed pulses,

(2) counter means connected to said pulse generator for counting said pulses, and

(3) trigger means connected to said electrodes and responsive to said predetermined resistance for disconnecting said counter means from said pulse generator.

2. An apparatus for determining the erythrocyte sedimentation rate of blood comprising, in combination:

(a) a vertically elongated container adapted to contain said blood;

(b) two electrodes;

(c) mounting means mounting said electrodes in said container at predetermined vertically spaced levels;

(d) signal generating means responsive to a predetermined electrical resistance between said electrode for generating a signal; and

(e) temperature compensating means connected to said signal generating means for varying said predetermined resistance responsive to ambient temperature.

3. An apparatus for determining the erythrocyte sedimentation rate of blood comprising, in combination:

(a) two electrodes;

(b) mounting means for mounting said electrodes in a container containing said blood at predetermined vertically spaced levels; and

(c) signal generating means responsive to a predetermined electrical resistance between said electrodes for generating a signal, said signal generating means including timing means, and trigger means responsive to said predetermined resistance for arresting said timing means.

4. An apparatus for determining the erythrocyte sedimentation rate of blood comprising, in combination:

(a) two electrodes;

(b) mounting means for mounting said electrodes in a container containing said blood at predetermined vertically spaced levels;

(c) signal generating means responsive to a predetermined electrical resistance between said electrodes for generating a signal;

( d) a source of electric potential;

(e) a resistor in series circuit with said source and said electrodes, whereby said resistor and said blood when interposed between said electrodes constitute voltage divider means; and

(f) tap means interposed between said resistor and one of said electrodes, said tap means being connected to said signal generating means.

5. An apparatus as set forth in claim 4, wherein said resistor has a negative temperature coefficient.

6. A method of determining the erythrocyte sedimentation rate of blood which comprises permitting the erythrocytes of a specimen of said blood to sediment in the plasma of said specimen, and generating a signal responsive to a change in resistance between two vertically spaced portions of said specimen during the sedimentation of said erythrocytes.

7. A method as set forth in claim 6, wherein said signal is generated responsive to a decrease of said resistance to a predetermined value.

8. A method as set forth in claim 7, wherein said signal is indicative of the time elapsed between the beginning of said sedimentation and the decrease of said resistance to said predetermined value.

5 9. A method of determining the erythrocyte sedimentation rate of blood which comprises permitting the erythrocytes of a specimen of said blood to sediment in the plasma of said specimen, and generating a signal responsive to a change in resistance in a portion of said specimen during the sedimentation of said erythrocytes from the plasma in said specimen portion.

10. A method of determining the erythrocyte sedimentation rate of blood which comprises: 7

(a) causing the erythrocytes of a specimen of said blood to sediment in the plasma of said specimen; (b) sensing the electrical resistance of a portion of said specimen during the sedimentation of the erythrocytes in the plasma of said specimen portion; and (c) generating a perceptible signal responsive to a predetermined value of the sensed electrical resistance of said specimen portion. a

References Cited by the Examiner UNITED STATES PATENTS Witt 736l X Polanyi 7361 X LOUIS R. PRINCE, Primary Examiner.

DAVID SCHONBERG, Examiner.

Johnson 73-304 X 

1. AN APPARATUS FOR DETERMINING THE ERYTHROCYTE SEDIMENTATION RATE OF BLOOD COMPRISING, IN COMBINATION: (A) TWO ELECTRODES; (B) MOUNTING MEANS FOR MOUNTING SAID ELECTRODES IN A CONTAINER CONTAINING SAID BLOOD AT PREDETERMINED VERTICALLY SPACED LEVELS; AND (C) SIGNAL GENERATING MEANS RESPONSVIE TO A PREDETERMINED ELECTRICAL RESISTANCE BETWEEN SAID ELECTRODES FOR GENERARTING A SIGNAL, SAID SIGNAL GENERATING MEANS INCLUDING (1) A PULSE GENERATOR FOR GENERATING TIMED PULSES, (2) COUNTER MEANS CONNECTED TO SAID PULSE GENERATOR FOR COUNTING SAID PULSE, AND (3) TRIGGER MEANS CONNECTED TO SAID ELECTRODES AND RESPONSIVE TO SAID PREDETERMINED RESISTANCE FOR DISCONNECTING SAID COUNTER MEANS FOR SAID PULSE GENERATOR. 